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Epigenetics in cardiac development, function, and disease

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Abstract

Substantial new knowledge has accrued, over the past few years, concerning the epigenetic regulation of heart development and disease. Epigenetic mechanisms comprise DNA methylation, ATP-dependent chromatin remodeling, histone modifications, and non-coding RNAs. Many of these processes have been ascertained to influence the tight spatiotemporal control of gene expression during cardiac development. Nevertheless, the relative contribution of each mechanism and their potentially complex interplay remain largely unexplored. Cardiac development and disease are linked through the reactivation of fetal genes upon cardiac hypertrophy and failure. In cardiac disease, changes in gene expression are accompanied and influenced by distinct changes in histone modifications. Detailed knowledge about the epigenetic pathways of cardiac development and function is expected ultimately to lead to novel therapeutic strategies for heart disease and regenerative medicine.

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Abbreviations

Adamts1:

A disintegrin and metalloproteinase with thrombospondin motif

BAF:

BRG1/BRM-associated factor

Bmp10:

Bone morphogenetic protein 10

BRD:

Bromodomain

Brg1:

Brahma-related gene 1

Brm:

Brahma

CHD:

Chromodomain helicase DNA binding

Ctcf:

CCCTC-binding factor

Dnmt:

DNA methyltransferase

Dot1l:

DOT1-like histone H3 methyltransferase

Dpf3:

D4 zinc and double PHD fingers, family 3

Dux4:

Double homeobox 4

Ezh2:

Enhancer of zeste homolog 2

Fhl1:

Four-and-a-half LIM domains 1

Gata4:

GATA-binding protein 4

HAT:

Histone acetyltransferase

Hdac:

Histone deacteylase

Hp1:

Heterochromatin protein 1

INO80:

Inositol requiring 80

ISWI:

Imitation switch

Jmjd3:

Jumonji-domain-containing 3 histone lysine demethylase 3

Kap1:

Kinesin-II-associated protein

Kdm4a:

Lysine (K)-specific demethylase 4A

Lsd1:

Lysine (K)-specific demethylase 1A

MBD:

Methyl-CpG-binding domain

Mef2a,c:

Myocyte enhancer factor 2A,C

Myh6:

α-Myosin heavy chain

Myh7:

β-Myosin heavy chain

MYST:

Moz Ybf2/Sas3, Sas2, Tip60

NCoR:

Nuclear receptor corepressor

Nkx2-5:

NK2 homeobox 5

Nppa:

Atrial natriuretic peptide ANP

Nppb:

Brain natriuretic peptide BNP

NURD:

Nucleosome remodeling and histone deacetylase

Parp-1:

Poly (ADP-ribose) polymerase 1

PBAF:

Polybromo Brg1-associated factors

PRC2:

Polycomb repressive complex 2

SET:

Su(var)3–9 enhancer of zeste, trithorax

Sir2:

Silent information regulator-2

Six1:

Homeobox protein SIX1

Smarca:

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member

Smrt:

Silencing mediator of retinoic acid and thyroid hormone receptor

Smyd1:

SET and MYND domain containing 1

SNPs:

Single nucleotide polymorphisms

SRA:

SET and ring-associated

Suv39h1:

Suppressor of variegation 3–9 homolog 1

SWI/SNF:

Switching defective/sucrose nonfermenting

Tet:

Ten-eleven translocation methylcytosine dioxygenase

Tnnt2:

Cardiac troponin T type 2

Uhrf1,2:

Ubiquitin-like with PHD and ring finger domain 1,2

Utx:

Ubiquitously transcribed tetratricopeptide repeat X chromosome

Whsc1:

Wolf-Hirschhorn syndrome candidate 1

Wnt5a:

Wingless-related MMTV integration site 5A

Zbtb:

Zinc finger and BTB domain containing

Zfp57:

ZFP57 zinc finger protein

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  1. Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, Albertstrasse 25, 79104, Freiburg, Germany

    Thomas Nührenberg, Ralf Gilsbach, Sebastian Preissl, Tilman Schnick & Lutz Hein

  2. University Heart Center Freiburg Bad Krozingen, University of Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany

    Tilman Schnick

  3. Hermann Staudinger Graduate School, University of Freiburg, Albertstrasse 21, 79104, Freiburg, Germany

    Sebastian Preissl

  4. BIOSS Centre for Biological Signalling Studies, University of Freiburg, Schänzlestrasse 18, 79104, Freiburg, Germany

    Lutz Hein

  5. Department of Cardiology and Angiology II, University Heart Center Freiburg Bad Krozigen, Südring 15, 79189, Bad Krozigen, Germany

    Thomas Nührenberg

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Nührenberg, T., Gilsbach, R., Preissl, S. et al. Epigenetics in cardiac development, function, and disease. Cell Tissue Res 356, 585–600 (2014). https://doi.org/10.1007/s00441-014-1887-8

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